Perales-Clemente Ester, Folmes Clifford D L, Terzic Andre
Center for Regenerative Medicine, Mayo Clinic , Rochester, Minnesota.
Antioxid Redox Signal. 2014 Oct 10;21(11):1648-59. doi: 10.1089/ars.2014.6000. Epub 2014 Sep 4.
Metabolism-dependent generation of reactive oxygen species (ROS) and associated oxidative damage have been traditionally linked to impaired homeostasis and cellular death. Beyond the adverse effects of ROS accumulation, increasing evidence implicates redox status as a regulator of vital cellular processes.
Emerging studies on the molecular mechanisms guiding stem cell fate decisions indicate a role for energy metabolism in regulating the fundamental ability of maintaining stemness versus undergoing lineage-specific differentiation. Stem cells have evolved protective metabolic phenotypes to minimize reactive oxygen generation through oxidative metabolism and support antioxidant scavenging through glycolysis and the pentose phosphate pathway.
While the dynamics in ROS generation has been correlated with stem cell function, the intimate mechanisms by which energy metabolism regulates ROS to impact cellular fate remain to be deciphered.
Decoding the linkage between nutrient sensing, energy metabolism, and ROS in regulating cell fate decisions would offer a redox-dependent strategy to regulate stemness and lineage specification.
传统上，依赖代谢产生的活性氧（ROS）及相关氧化损伤与体内稳态受损和细胞死亡有关。除了ROS积累的不利影响外，越来越多的证据表明氧化还原状态是重要细胞过程的调节因子。
关于指导干细胞命运决定的分子机制的新兴研究表明，能量代谢在调节维持干性与进行谱系特异性分化的基本能力方面发挥作用。干细胞已经进化出保护性代谢表型，以通过氧化代谢将活性氧生成降至最低，并通过糖酵解和磷酸戊糖途径支持抗氧化清除。
虽然活性氧生成的动态变化与干细胞功能相关，但能量代谢调节活性氧以影响细胞命运的具体机制仍有待阐明。
解读营养感知、能量代谢和活性氧在调节细胞命运决定中的联系，将为调节干性和谱系特化提供一种依赖氧化还原的策略。
